TTN : c.3884C>T

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.3884C>T	p.S1295L (Ser > Leu)	substitution	missense	chr2:179644035 (reverse strand)	0.96057697

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.96057697 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

The role on non-truncating TTN variants in cardiac disease has not yet been analysed in these studies.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.98904036 65878 / 66608	0.86864571 8954 / 10308	0.87660219 7523 / 8582	0.95830303 15812 / 16500	0.93221221 10754 / 11536	0.98092643 6480 / 6606	0.96357616 873 / 906	0.96057697 116274 / 121046
ESP	0.99139 8524 / 8598	0.87177 3841 / 4406						0.95086 12365 / 13004
1KG	0.99381 803 / 808	0.84947 1123 / 1322	0.88294 890 / 1008	0.95910 938 / 978	0.94957 659 / 694	0.98485 195 / 198		0.92013 4608 / 5008

View sub-population details for 1000 Genomes (1KG) data

Hide sub-population details for 1000 Genomes (1KG) data

0.98901 180 / 182 British	0.87705 107 / 122 African-American	0.91398 170 / 186 Chinese Dai	0.94767 163 / 172 Bengali	0.95745 180 / 188 Colombian
0.99533 213 / 214 Iberian	0.85938 165 / 192 African-Caribbean	0.89806 185 / 206 Han, Beijing	0.97573 201 / 206 Gujarati Indian	0.91406 117 / 128 Mexican, LA
0.99065 212 / 214 Toscani	0.82323 163 / 198 Esan, Nigeria	0.81250 169 / 208 Japanese	0.95588 195 / 204 Indian Telugu	0.96471 164 / 170 Peruvian
1.00000 198 / 198 Utah Europeans	0.84513 191 / 226 Gambian	0.88384 175 / 198 Kinh, Vietnam	0.94792 182 / 192 Punjabi, Lahore	0.95192 198 / 208 Puerto Rican
	0.83333 165 / 198 Luhya, Kenya	0.90952 191 / 210 Southern Han	0.96569 197 / 204 Tamil
	0.84118 143 / 170 Mende
	0.87500 189 / 216 Yoruba, Nigeria

The Exome Aggregation Consortium (ExAC) is a database of 60,706 unrelated individuals sequenced as part of various disease-specific and population genetic studies. There is partial overlap between ExAC and 1000 Genomes (1KG) (1,851 of the 2,504 samples in 1KG) and the Exome Sequencing Project (ESP) (3,936 of the 6,500 samples in ESP).

Other Variant & Gene Details

Canonical Sequences
Transcript	ENST00000589042	LRG_391t1	NM_001267550.1
Protein	ENSP00000467141	LRG_391p1

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 25% of algorithms have predicted that this variant will adversely affect protein function
damaging	moderately radical	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
	polymorphism (auto)	neutral	tolerated

References

1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.

3. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.